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EVALUATION OF PROGNOSIS AND EFFICACY OF THERAPY FOR NEUROBLASTOMA PATIENTS BY QUANTIFICATION OF METHYLATED DCR2 GENE PROMOTER IN SERUM DNA

通过定量血清 DNA 中甲基化 DCR2 基因启动子来评估神经母细胞瘤患者的预后和治疗效果

基本信息

批准号：
18390300
负责人：
HOSOI Hajime
金额：
$ 5.77万
依托单位：
Kyoto Prefectural University of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390300/
关键词：
Neurnhlastnma DCR2 aberrant methvlation real-time PCR serum DNA DCR2メチレーション Real-time PCR 微小残存腫瘍

项目摘要

Background: Detection of tumor specific epigenetic alterations using serum DNA has been reported as a reliable and non-invasive strategy for tumor assessment, especially for pediatric cancer patients who cannot easily undergo an invasive examination, because serum DNA predominantly originates from tumor-released DNA in cancer patients. Aberrant hypermethylation of the DCR2 gene (DCR2) promoter has attracted increasing attention because of its close association with rapidly progressing neuroblastomas (NB). Here, we assessed the utility of DCR2 promoter metbylation status as a prognostic factor and indicator of therapeutic efficacy in NB patients using their serum DNA.Methods: We evaluated the ratio of a methylated-DCR2 specific sequence (MVI) and a reference sequence (R) located in the DCR2 promoter in 86 NBs, 18 of which bad MYCN amplification (MNA) using their serum and tumor DNAResults: Serum DCR2 M/R ratios were strongly correlated with those in the tumor (r=0.67;p=0.002). DCR2 hypermethylation was associated with stage both in the whole NB group and in the non-MNA NB group (p<0.001),and patients with DCR2 hypermethylation showed significantly poorer 5-year EFS both in the whole NB group (43% vs. 84%; p<0.001) and in the non-MNA group (12% vs. 96%; p<0.001). Among 5 DCR2-methylated patients whose clinic-Al courses were followed, serum M/R ratios were dose to zero in the patients that experienced remission, whereas they greatly increased in the relapsed patients.Conclusions: Serum DCR2 methylation status is a useful biomarker for predicting a poor prognosis and determining therapeutic efficacy in NB, especially in non-MNANB patients. This method will help to identify NB patients with a poor prognosis, to determine the appropriate intensity of chemotherapy and to evaluate novel therapies.

背景资料：使用血清DNA检测肿瘤特异性表观遗传改变已被报道为用于肿瘤评估的可靠且非侵入性的策略，特别是对于不能容易地进行侵入性检查的儿科癌症患者，因为血清DNA主要来源于癌症患者中肿瘤释放的DNA。由于DCR 2基因启动子异常甲基化与神经母细胞瘤（NB）的快速进展密切相关，DCR 2基因启动子异常甲基化已引起越来越多的关注。在此，我们评估了DCR 2启动子甲基化状态作为NB患者预后因子和疗效指标的实用性，使用其血清DNA。方法：我们评估了86个NB中甲基化-DCR 2特异性序列（MVI）和位于DCR 2启动子中的参考序列（R）的比例，其中18个使用其血清和肿瘤DNA进行了不良MYCN扩增（MNA）。血清DCR 2 M/R比值与肿瘤中的比值密切相关（r=0.67;p=0.002）。在整个NB组和非MNA NB组中，DCR 2高甲基化与分期相关（p<0.001），并且在整个NB组（43% vs. 84%; p<0.001）和非MNA组（12% vs. 96%; p<0.001）中，DCR 2高甲基化患者的5年EFS显著较差。在5例DCR 2甲基化患者的临床-Al课程进行了跟踪，血清M/R比值剂量为零的患者经历缓解，而他们大大增加复发patients.Conclusions：血清DCR 2甲基化状态是一个有用的生物标志物，用于预测预后不良，并确定在NB的治疗效果，特别是在非MNANB患者。这种方法将有助于识别预后不良的NB患者，以确定适当的化疗强度和评估新的治疗方法。